کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2144826 1548026 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification and analysis of the human hyaluronan synthase 1 gene promoter reveals Smad3- and Sp3-mediated transcriptional induction
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Identification and analysis of the human hyaluronan synthase 1 gene promoter reveals Smad3- and Sp3-mediated transcriptional induction
چکیده انگلیسی

The ubiquitous mammalian extracellular matrix glycosaminoglycan hyaluronan (HA) plays a pivotal role in the regulation of cell phenotype in fibrosis and scarring. Transforming growth factor-beta 1 (TGF-β1) and interleukin-1 beta (IL-1β) up-regulate hyaluronan synthase (HAS) 1 and HAS2 in dermal fibroblasts and renal proximal tubular epithelial cells, and subsequent HA synthesis regulates cell phenotype. In the present study, we investigated the mechanism of HAS1 transcriptional up-regulation in response to these cytokines. We used 5′-rapid amplification of cDNA ends analysis to identify the 5′ end of HAS1 transcripts, resulting in an increase of 26 nucleotides to the HAS1 exon 1 sequence of reference sequence NM_001523. Constitutive luciferase activity of upstream DNA sequences was shown in luciferase reporter assays, but our reporter vector signals were refractory to the addition of TGF-β1 and IL-1β. Using siRNAs to knockdown transcription factor mRNAs, we showed that TGF-β1 up-regulation of HAS1 transcription was mediated via Smad3 but not Smad2, while HAS1 induction by IL-1β was Sp3, not Sp1, dependent.


► We identified the human HAS1 transcription start site upstream of NM_001523.
► The extended HAS1 5′-UTR is expressed throughout human tissues.
► In dermal fibroblasts, HAS1 transcriptional induction by TGF-β1 is Smad3-dependent.
► In dermal fibroblasts, HAS1 transcriptional induction by IL-1β is Sp3-dependent.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Matrix Biology - Volume 31, Issues 7–8, September–October 2012, Pages 373–379
نویسندگان
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